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Faculty
 Xuejun
(June) Li
Assistant Professor of Neuroscience
xjli@uchc.edu
Areas of Interest:
Stem cells; neural development and degeneration.
Human embryonic stem cells (hESCs), which are derived from the inner
cell mass of a pre-implantation embryo, have the capacity to become all
cell types in the body, including neurons. They thus provide an
invaluable tool for studying early human neural development and
exploring the potential treatment of neurological diseases.
The first line of our research is to specify neuronal subtypes from
human ESCs. By applying a set of morphogens in a specific time window,
we now have a model system for efficiently generating spinal motor
neurons from hESCs. Another type of motor neuron, cortical motor neuron,
is specified by a very different mechanism than spinal motor neurons in
animal models. However, no cortical motor neurons have been successfully
specified from hESCs. Here experiments are underway to generate
telencephalic neuronal subtypes including cortical motor neurons from
hESCs using epigenetic approaches and genetic modifications.
Another line of our research is to model neuronal degeneration in spinal
muscular atrophy (SMA) by using hESCs as an experimental system. SMA is
caused by the mutation of a single gene (survival of motor neuron, SMN)
and subsequent reduced levels of SMN protein. To achieve this, we will
first establish stable hESC lines with a deficiency in SMN protein
levels through RNA interference and lentiviral delivery. Spinal motor
neurons will then be differentiated from these hESC lines and assayed
for a variety of functional changes. Successful establishment of this
human cell model will provide a unique platform of high-throughput drug
screening for this debilitating and fatal genetic disorder.
This image shows the hESC-derived
spinal motor neurons, which are positive for HB9 (a motor neuron
specific marker, red) and βIII-tubulin (a
neuronal maker, green). Blue indicates Hoechst-stained nuclei.
[copyrighted and used with permission of the University of Wisconsin
Board of Regents]
Lab Rotation Projects:
Our laboratory is studying neural differentiation and degeneration
using human embryonic stem cells as an experimental system. Rotation
students in the lab will have the opportunity to learn a variety of
techniques, including but not limited to: stem cell culture, motor
neuron differentiation from hESCs, genetic modification of stem cells,
immunohistochemistry, confocal microscopy and quantitative PCR. Possible
rotation projects include:
1. Generation of telencephalic glutamatergic and GABAergic neurons
from hESCs.
2. Modeling motor neuron degeneration of spinal muscular atrophy using
hESCs.
Selected Publications:
LI XJ, Hu BY, Jones SA, Zhang YS, Du ZW, Zhang SC. Directed
differentiation of ventral spinal progenitors and motor neurons from
human embryonic stem cells by small molecules. Stem Cells. In press.
Li XJ, Yang DL, Zhang SC. Motoneuron and dopamine neuron
differentiation. In: Loring J, Wesselschmidt R, Schwartz P. eds. Human
Stem Cell Manual: a Laboratory Guide. Spiral Bound, 2008.
Zhang SC, Li XJ, Johnson MA, Pankratz M. Human embryonic stem cells
for brain repair (review). Philosophical Transactions: Biological
Sciences. 2008, 363:87-99.
Pankratz MT, Li XJ, Lavaute TM, Lyons EA, Chen X, Zhang SC. Directed
Neural Differentiation of hESCs via an Obligated Primitive Anterior
Stage. Stem Cells. 2007, 25:1511-1520.
Li XJ, Zhang SC. In vitro differentiation of neural precursors from
human embryonic stem cells. Methods Mol. Biol. 2006, 331:169-77.
Du ZW, Li XJ, Nguyen GD, Zhang SC. Induced expression of Olig2 is
sufficient for oligodendrocyte specification but not for motoneuron
specification and astrocyte repression. Mol. Cell. Neurosci. 2006,
33:371-380.
Li XJ, Du ZW, Zarnowska ED, Pankratz M, Hansen LO, Pearce RA, Zhang
SC. Specification of motoneurons from human embryonic stem cells. Nature
Biotechnol. 2005, 23: 215-221. rev 3-08 |
